Chapter 18
The Endocrine System
Endocrine and nervous systems work together
Endocrine system
hormones released into the
bloodstream travel throughout the body
results may take hours, but last
longer
Nervous system
certain parts release hormones into
blood
rest releases neurotransmitters
excite or inhibit nerve, muscle & gland cells
results in milliseconds, brief
duration of effects
General Functions of Hormones
Help regulate:
extracellular
fluid
metabolism
biological clock
contraction of cardiac & smooth
muscle
glandular secretion
some immune functions
Growth & development
Reproduction
Endocrine Glands Defined
Exocrine glands
secrete products into ducts which
empty into body cavities or body surface
sweat, oil, mucous, & digestive
glands
Endocrine glands
secrete products (hormones) into
bloodstream
pituitary, thyroid, parathyroid,
adrenal, pineal
other organs secrete hormones as a
2nd function
hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach, liver, small
intestine, skin, heart & placenta
Hormone Receptors
Hormones only affect target cells with specific membrane
proteins called receptors
Role of Hormone Receptors
Constantly being synthesized & broken down
A range of 2000-100,000 receptors / target cell
Down-regulation
excess hormone, produces a decrease
in number of receptors
receptors undergo endocytosis and are degraded
decreases sensitivity of target
cell to hormone
Up-regulation
deficiency of hormone, produces an
increase in the number of receptors
target tissue more sensitive to the
hormone
Blocking Hormone Receptors
Synthetic hormones that block receptors for naturally
occurring hormones
RU486 (mifepristone) binds to the
receptors for progesterone preventing it from maintaining the uterus in a
pregnant woman
used to induce abortion
brings on menstrual cycle
Hormone is prevented from interacting with its receptors and
can not perform its normal functions
Circulating & Local Hormones
Circulating hormones
act on distant targets
travel in blood
Local hormones
paracrines
act on neighboring cells
autocrines
act on same cell that secreted them
Lipid-soluble Hormones
Steroids
lipids derived from cholesterol on
SER
different functional groups
attached to core of structure provide uniqueness
Thyroid hormones
tyrosine ring plus attached iodines are lipid-soluble
Nitric oxide is gas
Water-soluble Hormones
Amine, peptide and protein hormones
modified amino acids or amino acids
put together
serotonin, melatonin, histamine,
epinephrine
some glycoproteins
Eicosanoids
prostaglandins
Hormone Transport in Blood
Protein hormones circulate in free form in blood
Steroid (lipid) & thyroid hormones must attach to
transport proteins synthesized by liver
General Mechanisms of Hormone Action
Hormone binds to cell surface or receptor inside target cell
Cell may then
synthesize
new molecules
change
permeability of membrane
alter
rates of reactions
Each target cell responds to hormone differently
liver cells---insulin stimulates
glycogen synthesis
adipose---insulin stimulates
triglyceride synthesis
Action of Lipid-Soluble Hormones
Hormone diffuses through phospholipid
bilayer & into cell
Binds to receptor turning on/off specific genes
New mRNA is formed & directs synthesis of new proteins
New protein alters cell’s activity
Action of Water-Soluble Hormones
Can not diffuse through plasma membrane
Hormone receptors are integral membrane proteins
act as first messenger
Amplification of Hormone Effects
Single molecule of hormone binds to receptor
One molecule of epinephrine may result in breakdown of
millions of glycogen molecules into glucose molecules
Cholera Toxin and G Proteins
Toxin is deadly because it produces massive watery diarrhea
and person dies from dehydration
Cyclic AMP causes intestinal cells to actively transport
chloride (Na+ and water follow) into the lumen
Person die unless ions and fluids
are replaced & receive antibiotic treatment
Hormonal Interactions
Permissive effect
a second hormone, strengthens the
effects of the first
thyroid strengthens epinephrine’s
effect upon lipolysis
Synergistic effect
two hormones acting together for
greater effect
estrogen & LH are both needed
for oocyte production
Antagonistic effects
two hormones with opposite effects
insulin promotes glycogen formation
& glucagon stimulates glycogen breakdown
Control of Hormone Secretion
Regulated by signals from nervous system, chemical changes
in the blood or by other hormones
Negative feedback control (most common)
decrease/increase in blood level is
reversed
Positive feedback control
the change produced by the hormone
causes more hormone to be released
Disorders involve either hyposecretion
or hypersecretion of a hormone
Negative Feedback Systems
Decrease in blood levels
Receptors in hypothalamus & thyroid
Cells activated to secrete more TSH or more T3 & T4
Blood levels increase
Positive Feedback
Oxytocin stimulates uterine
contractions
Uterine contractions stimulate oxytocin
release
Hypothalamus and Pituitary Gland
Both are master endocrine glands since their hormones
control other endocrine glands
Hypothalamus is a section of brain above where pituitary
gland is suspended from stalk
Hypothalamus receives input from cortex, thalamus, limbic
system & internal organs
Hypothalamus controls pituitary gland with 9 different
releasing & inhibiting hormones
Anatomy of Pituitary Gland
Pea-shaped, 1/2 inch gland found in sella
turcica of sphenoid
Anterior lobe = 75%
Posterior lobe = 25%
ends of axons of 10,000 neurons
found in hypothalamus
Flow of Blood to Anterior Pituitary
Controlling hormones enter blood
Travel through portal veins
Enter anterior pituitary at capillaries
Human Growth Hormone
Produced by somatotrophs
Within target cells increases synthesis of insulinlike growth factors that act locally or enter
bloodstream
common target cells are liver,
skeletal muscle, cartilage and bone
increases cell growth & cell
division by increasing their uptake of amino acids & synthesis of proteins
stimulate lipolysis
in adipose so fatty acids used for ATP
retard use of glucose for ATP
production so blood glucose levels remain high enough to supply brain
Regulation of hGH
Low blood sugar stimulates release of GNRH from hypothalamus
anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells
High blood sugar stimulates release of GHIH from
hypothalamus
less hGH
from anterior pituitary, glycogen does not breakdown into glucose
Diabetogenic Effect of Human
Growth Hormone
Excess of growth hormone
raises blood glucose concentration
pancreas releases insulin
continually
beta-cell burnout
Diabetogenic effect
causes diabetes mellitis
if no insulin activity can occur eventually
Thyroid Stimulating Hormone (TSH)
Hypothalamus regulates thyrotroph
cells
Thyrotroph cells produce TSH
TSH stimulates the synthesis & secretion of T3 and T4
Metabolic rate stimulated
Follicle Stimulating Hormone (FSH)
Releasing hormone from hypothalamus
controls gonadotrophs
Gonadotrophs release
follicle stimulating hormone
FSH functions
initiates the formation of
follicles within the ovary
stimulates follicle cells to
secrete estrogen
stimulates sperm production in
testes
Luteinizing Hormone (LH)
Releasing hormones from hypothalamus stimulate gonadotrophs
Gonadotrophs produce LH
In females, LH stimulates
secretion of estrogen
ovulation of 2nd oocyte from ovary
formation of corpus luteum
secretion of progesterone
In males, stimulates interstitial cells to secrete
testosterone
Prolactin (PRL)
Hypothalamus regulates lactotroph
cells
Lactotrophs produce prolactin
Under right conditions, prolactin causes milk production
Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production
Nursing ceases & milk production slows
Adrenocorticotrophic Hormone
Hypothalamus releasing hormones stimulate corticotrophs
Corticotrophs secrete ACTH &
MSH
ACTH stimulates cells of the adrenal cortex that produce glucocorticoids
Melanocyte-Stimulating Hormone
Secreted by corticotroph cells
Releasing hormone from hypothalamus increases its release From the anterior pituitary
Function not certain in humans (increase skin pigmentation
in frogs )
Posterior Pituitary Gland (Neurohypophysis)
Does not synthesize hormones
Consists of axon terminals of hypothalamic neurons
Neurons release two neurotransmitters that enter capillaries
antidiuretic
hormone
oxytocin
Oxytocin
Two target tissues both involved in neuroendocrine
reflexes
During delivery
baby’s head stretches cervix
hormone release enhances uterine
muscle contraction
baby & placenta are delivered
After delivery
suckling & hearing baby’s cry
stimulates milk ejection
hormone causes muscle contraction
& milk ejection
Oxytocin during Labor
Stimulation of uterus by baby
Hormone release from posterior pituitary
Uterine smooth muscle contracts until birth of baby
Baby pushed into cervix, increase hormone release
More muscle contraction occurs
When baby is born, positive feedback ceases
Antidiuretic Hormone (ADH)
Known as vasopressin
Functions
decrease urine production
decrease sweating
increase BP
Regulation of ADH
Dehydration
ADH released
Overhydration
ADH inhibited
Thyroid Gland
On each side of trachea is lobe of thyroid
Weighs 1 oz & has rich blood supply
Photomicrograph of Thyroid Gland
Actions of Thyroid Hormones
T3 & T4 = thyroid hormones responsible for our metabolic
rate, synthesis of protein, breakdown of fats, use of glucose for ATP
production
Calcitonin = responsible for
building of bone & stops reabsorption of bone
(lower blood levels of Calcium)
Control of T3 & T4 Secretion
Negative feedback system
Low blood levels of hormones stimulate hypothalamus
It stimulates pituitary to release TSH
TSH stimulates gland to raise blood levels
Parathyroid Glands
4 pea-sized glands found on back of thyroid gland
Parathyroid Hormone
Raise blood calcium levels
increase activity of osteoclasts
increases reabsorption
of Ca+2 by kidney
promote formation of calcitriol (vitamin D3) by kidney which increases
absorption of Ca+2 and Mg+2 by intestinal tract
Opposite function of calcitonin
Regulation of Calcium Blood Levels
High or low blood levels of Ca+2 stimulate the release of
different hormones --- PTH or CT
Adrenal Glands
One on top of each kidney
3 x 3 x 1 cm in size and weighs 5 grams
Cortex produces 3 different types of hormones from 3
zones of cortex
Medulla produces epinephrine & norepinephrine
Structure of Adrenal Gland
Cortex derived from mesoderm
Medulla derived from ectoderm
Regulation of Aldosterone
Glucocorticoids
95% of hormonal activity is due to cortisol
Functions = help regulate metabolism
increase rate of protein catabolism
& lipolysis
conversion of amino acids to
glucose
stimulate lipolysis
provide resistance to stress by
making nutrients available for ATP production
raise BP by vasoconstriction
anti-inflammatory effects reduced
(skin cream)
reduce release of histamine from
mast cells
decrease capillary permeability
depress phagocytosis
Regulation of Glucocorticoids
Negative feedback
Androgens from Zona Reticularis
Small amount of male hormone produced
insignificant in males
may contribute to sex drive in
females
is converted to estrogen in
postmenopausal females
Adrenal Medulla
Chromaffin cells receive direct innervation from sympathetic nervous system
develop from same tissue as
postganglionic neurons
Produce epinephrine & norepinephrine
Hormones are sympathomimetic
effects mimic those of sympathetic
NS
cause fight-flight behavior
Acetylcholine increase hormone secretion by adrenal medulla
Anatomy of Pancreas
Organ (5 inches) consists of head, body & tail
Cells (99%) in acini produce
digestive enzymes
Endocrine cells in pancreatic islets produce hormones
Cell Types in the Pancreatic Islets
Alpha cells (20%) produce glucagon
Beta cells (70%) produce insulin
Delta cells (5%) produce somatostatin
F cells produce pancreatic polypeptide
Regulation of Glucagon &
Insulin Secretion
Low blood glucose stimulates release of glucagon
High blood glucose stimulates secretion of insulin
Ovaries and Testes
Ovaries
estrogen, progesterone, relaxin & inhibin
regulate reproductive cycle,
maintain pregnancy & prepare mammary glands for lactation
Testes
produce testosterone
regulate sperm production & 2nd
sexual characteristics
Pineal Gland
Small gland attached to 3rd ventricle of brain
Melatonin responsible for setting of biological clock
Jet lag & SAD treatment is bright light
Effect of Light on Pineal Gland
Melatonin secretion producing sleepiness occurs during
darkness due to lack of stimulation from sympathetic ganglion
Seasonal Affective Disorder and Jet Lag
Depression that occurs during winter months when day length
is short
Due to overproduction of melatonin
Therapy
exposure to several hours per day
of artificial light as bright as sunlight
speeds recovery from jet lag
Thymus Gland
Important role in maturation of T cells
Hormones produced by gland promote the proliferation &
maturation of T cells
thymosin
thymic humoral factor
thymic
factor
thymopoietin
Miscellaneous Hormones Eicosanoids
Local hormones released by all body cells
Leukotrienes influence WBCs & inflammation
Prostaglandins alter
smooth muscle contraction,
glandular secretion, blood flow, platelet function, nerve transmission,
metabolism etc.
Ibuprofen & other nonsteroidal
anti-inflammatory drugs treat pain, fever & inflammation by inhibiting
prostaglandin synthesis
Nonsteroidal Anti-inflammatory
Drugs
Answer to how aspirin or ibuprofen works was discovered in
1971
inhibit a key enzyme in
prostaglandin synthesis without affecting the synthesis of leukotrienes
Treat a variety of inflammatory disorders
rheumatoid arthritis
Usefulness of aspirin to treat fever & pain implies
prostaglandins are responsible for those symptoms
Growth Factors
Substances with mitogenic
qualities
cause cell growth from cell
division
Many act locally as autocrines or paracrines
Selected list of growth factors (Table 18.12)
epidermal growth factor
platelet-derived growth factor
fibroblast growth factor
nerve growth factor
tumor angiogenesis factors
transforming growth factors
Stress & General Adaptation Syndrome
Stress response is set of bodily changes called general
adaptation syndrome (GAS)
Any stimulus that produces a stress response is called a
stressor
Stress resets the body to meet an emergency
eustress
is productive stress & helps us prepare for certain challenges
distress type levels of stress are
harmful
lower our resistance to infection
Alarm Reaction (Fight-or-Flight)
Initiated by hypothalamic stimulation of sympathetic portion
of the ANS & adrenal medulla
Dog attack
increases circulation
promotes ATP synthesis
nonessential body functions are
inhibited
digestive, urinary &
reproductive
Resistance Reaction
Initiated by hypothalamic releasing hormones (long-term
reaction to stress)
corticotropin,
growth hormone & thyrotropin releasing hormones
Results
increased secretion of aldosterone acts to conserve Na+ (increases blood pressure)
and eliminate H+
increased secretion of cortisol so protein catabolism is increased & other
sources of glucose are found
increase thyroid hormone to
increase metabolism
Allow body to continue to fight a stressor
Exhaustion
Resources of the body have become depleted
Resistance stage can not be maintained
Prolonged exposure to resistance reaction hormones
wasting of muscle
suppression of immune system
ulceration of the GI tract
failure of the pancreatic beta
cells
Stress and Disease
Stress can lead to disease by inhibiting the immune system
hypertension, asthma, migraine,
gastritis, colitis, and depression
Interleukin - 1 is secreted by macrophages
link between stress and immunity
stimulates production of immune
substances
feedback control since immune
substance suppress the formation of interleukin-1
Aging and the Endocrine System
Production of human growth hormone decreases
muscle atrophy
Production of TSH increase with age to try and stimulate
thyroid
decrease in metabolic rate,
increase in body fat & hypothyroidism
Thymus after puberty is replaced with adipose
Adrenal glands produce less cortisol
& aldosterone
Receptor sensitivity to glucose declines
Ovaries no longer respond to gonadotropins
decreased output of estrogen
(osteoporosis & atherosclerosis)
Pituitary Gland Disorders
Hyposecretion during childhood =
pituitary dwarfism (proportional,
childlike body)
Hypersecretion during childhood = giantism
very tall, normal proportions
Hypersecretion as adult = acromegaly
growth of hands, feet, facial
features & thickening of skin
Thyroid Gland Disorders
Hyposecretion during infancy
results in dwarfism & retardation called cretinism
Hypothyroidism in adult produces sensitivity to cold, low
body temp. weight gain & mental dullness
Hyperthyroidism (Grave’s disease)
weight loss, nervousness, tremor
& exophthalmos (edema behind eyes)
Goiter = enlarged thyroid (dietary)
Cushing’s Syndrome
Hypersecretion of glucocorticoids
Redistribution of fat, spindly arms & legs due to muscle
loss
Wound healing is poor, bruise easily
Addison’s disease
Hypersecretion of glucocorticoids
hypoglycemia, muscle weakness, low
BP, dehydration due to decreased Na+ in blood
mimics skin darkening effects of
MSH
potential cardiac arrest
Diabetes Mellitus & Hyperinsulinism
Diabetes mellitus marked by hyperglycemia
excessive urine production (polyuria)
excessive thirst (polydipsia)
excessive eating (polyphagia)
Type I----deficiency of insulin (under 20)
Type II---adult onset
drug stimulates secretion of
insulin by beta cells
cells may be less sensitive to
hormone